Heart Failure HANDOUT 2024 PDF

Jeffrey F. Barletta, Pharm.D., FCCM Professor & Vice Chair Department of Pharmacy Practice Office: Cholla 201-11 Phone: 623-572-3547  Describe the key hemodynamic parameters and their relevance in a patient with ADHF.  Describe the four hemodynamic subsets for acut...

Jeffrey F. Barletta, Pharm.D., FCCM Professor & Vice Chair Department of Pharmacy Practice Office: Cholla 201-11 Phone: 623-572-3547  Describe the key hemodynamic parameters and their relevance in a patient with ADHF.  Describe the four hemodynamic subsets for acute decompensated heart failure  Select the type of heart failure according to the 4 hemodynamic subsets given laboratory values and a patient presentation  Develop a pharmacotherapy-related treatment plan for a patient with ADHF.  Develop a plan for diuretic therapy in a patient with ADHF.  Describe the role of vasodilator therapy in a patient with ADHF.  Describe the role of inotropic therapy in a patient with ADHF.  Reed BN, et al. Acute Decompensated Heart Failure. In: DiPiro et al. eds. Pharmacotherapy: A Pathophysiologic Approach, 12e New York, NY: McGraw-Hill. 2023  McDonagh, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599-3726.  Heidenreich, et al. 2022 AHA/ACC/HFSA Guideline for the management of heart failure. Circulation 2022;145;e895-1032  ADHF is new or worsening signs or symptoms of HF, often as a result of volume overload and/or low CO  Goals of therapy somewhat different than chronic HF: ◦ Hemodynamic stabilization ◦ Symptom relief ◦ Prevention of short-term morbidity/mortality  Worsening chronic heart failure ◦ Nonadherence to medications ◦ Medications that increase sodium retention ◦ Medications with negative inotropic effect ◦ Dietary indiscretion ◦ Uncontrolled HTN ◦ Substance abuse ◦ Concurrent non-cardiac illness (e.g., infection, thyroid disorders, anemia)  New or worsening cardiac process ◦ ACS/MI ◦ Atrial fibrillation/other arrhythmia ◦ Hypertensive crisis  De novo heart failure Volume (“wet”) Perfusion (“cold”)  Pulmonary congestion  Hypotension  Edema  Cool extremities  Elevated jugular venous  Pallor pressure  Altered mental status  Fluid overload  Oliguria  Dyspnea  N/V  Orthopnea  Impaired end-organ perfusion  Weight gain  Ascites  Volume ◦ Central venous pressure (CVP): < 5 mmHg ◦ Pulmonary capillary wedge pressure (PCWP): < 12 mmHg  Pressure ◦ Systemic arterial pressure (BP): 120/80 mmHg ◦ Mean arterial pressure (MAP): 70-110 mmHg ◦ Pulmonary artery pressure (PAP): 25/10 mmHg ◦ Systemic vascular resistance (SVR): 800 – 1400 dyn.sec.cm-5  Output ◦ Cardiac output: 4 – 6 L/min ◦ Cardiac index: 2.8 – 4.2 L/min/m2 SVR = [MAP – CVP]*80 CO Key: Warm = perfused Subset I: Warm & Dry Subset II: Warm & Wet Warm Cold = hypoperfused Wet = volume overload Cardiac index Dry = not volume overload 2.2 Subset III: Cold & Dry Subset IV: Cold & Wet Cold Dry 18 Wet Pulmonary capillary wedge pressure  A 62-year-old patient with a PCWP of 28 and CI of 1.8.  A 72-year-old patient with a PCWP of 20 and a CI of 2.5  A 58-year-old patient presenting with orthopnea, dyspnea with minimal exertion, 3+ pitting edema, confusion and hypotension  A 78-year-old patient presenting with pulmonary crackles, JVD, low O2 saturation and tachycardia. Mentation is appropriate and extremities are warm to touch  Subset I: Subset II: Warm & Dry Warm & Wet Cardiac index 2.2 Subset III: Subset IV:  No signs or symptoms of volume overload Cold & Dry Cold & Wet  No signs or symptoms of hypoperfusion 18 Pulmonary capillary wedge pressure  Optimize chronic oral medications  Subset I: Subset II: Warm & Dry Warm & Wet Cardiac index 2.2 Subset III: Subset IV: Cold & Dry Cold & Wet IV Loop Diuretic 18 Pulmonary capillary wedge pressure +/- IV vasodilator Is dyspnea present? Is SBP elevated? Sodium restriction (2 – 3 gm/daily) Fluid restriction (< 2 L/day) Supplemental O2 as needed for hypoxemia  Clinical impact ◦ Reduced preload ◦ Improves pulmonary congestion ◦ No effect on mortality  Goals of therapy ◦ Resolve clinical evidence of congestion & reduce symptoms ◦ Most patients can tolerate a 2L/day net negative fluid status  Dosing ◦ Naïve patients: Furosemide 20 – 40 mg IV once to twice daily ◦ Patients on home diuretics: 1 to 2.5 x daily home dose, IV  Precautions ◦ Renal dysfunction ◦ Hypotension ◦ Electrolyte depletion  Furosemide Bumetanide Torsemide (Lasix®) (Bumex®) (Soaanz®) Usual bolus dose 20 to 160 mg 0.5 to 4 mg 10 to 80 mg Equivalent dose IV 40 mg 1 mg 10 to 20 mg IV to PO 1:2 1:1 1:1 Duration of action 6 hours 6 hours 6 – 8 hours DOSE Felker, et al. JACC 2020;75(10):1178-95. Low dose: equivalent to previous oral dose, IV High dose: 2.5 times the previous oral dose, IV Felker, et al. NEJM 2011;364:797-805. Mullens, et al. Eur Heart J 2019;21:137-55 Mullens, et al. Eur Heart J 2019;21:137-55  Mechanisms are multifactorial ◦ Diminished diuretic response in the loop of Henle ◦ Compensatory sodium reabsorption in the distal convoluted tubule ◦ Distal tubule hypertrophy ◦ Decreased renal perfusion from impaired CO  Strategies to overcome: ◦ Increase dose ◦ Continuous infusion ◦ Add a diuretic with an alternative mechanism of action  Metolazone (Zaroxolyn®) 2.5 – 5 mg po QD (thiazide-like)  Hydrochlorothiazide (Microzide®) 50 mg po QD (thiazide)  Chlorothiazide (Diuril®) 500 IV BID (thiazide)  5% of Na reabsorption 65-75% of Na reabsorption 25% of Na reabsorption  Diuretic doses should be guided by clinical response to initial doses  Urine output should measurably increase within 2 hours  Because the dose response curve is logarithmic, substantial increases (i.e., doubling) are required  Increases in SCr (up to 0.5 mg/dL) are common and do not necessitate stopping loop diuretics  Combination therapy leads to improvements in diuresis but also electrolyte abnormalities.  A 68 year old patient presents with ADHF. Staging is consistent with subset II. Furosemide 20 mg IV is administered x1 and urine output has increased about 15 ml/hour above baseline (30 ml/hr) for 3 hours. Her congestive symptoms have not improved. What do you recommend. A. Increase the dose to 40 mg IV B. Increase the dose to 40 mg po C. Add metolazone 5 mg daily D. Change to bumetanide 0.5 mg  A 72 year old patient presents with ADHF. Staging is consistent with subset II. She take furosemide 20 mg po BID at home but has a substantial amount of pulmonary congestion. What dose of diuretic do you recommend  There is an ongoing drug shortage and the institution does not have furosemide. What do you recommend.  Useful in patients with ADHF and hyponatremia (Na < 125) ◦ HF is commonly associated with hypervolemic hyponatremia ◦ Due to elevated concentrations of AVP or ADH  Work by antagonizing vasopressin receptors blocking water reabsorption at the collecting duct  Minimal benefit in clinical outcomes other than increases in serum Na, improved UOP and congestive symptoms Conivaptan Tolvaptan Receptor V1a and V2 V2 Route IV PO Metabolism 3A4 3A4  Clinical impact ◦ Restore tissue perfusion in patients with low CO ◦ Reduce preload by increasing venous capacitance (venous vasodilators) ◦ Reduce afterload and increase CO (arterial vasodilators) ◦ No effect on mortality  Goals of therapy ◦ Reduce pulmonary congestion ◦ Improve CO  Precautions ◦ Hypotension  Clinical use ◦ Preferred for preload reduction ◦ Primarily a venodilator (some arterial dilation occurs at high doses) ◦ Preferred if also ACS (coronary vasodilation)  Dosing ◦ Continuous infusion: Initiate at 5 – 10 mcg/min, titrate to effect (max, 200 mcg/min) ◦ Tolerance frequently occurs  Administration ◦ Dispense in glass or non-PVC container ◦ Special tubing  Adverse effects ◦ Headache ◦ Hypotension  Clinical use ◦ Both venous and arterial vasodilator ◦ Greater decreases in SVR and BP generally observed  Dosing: ◦ Continuous infusion: Initiate at 0.1 mcg/kg/min, titrate to effect (max, 3 mcg/kg/min)  Administration: protect from light  Adverse effects ◦ Cyanide toxicity: hepatic insufficiency or high infusion rates (>2 mcg/kg/min) ◦ Thiocyanate toxicity: renal insufficiency or prolonged infusions (>3 mcg/kg/min for > 3 days)  Compare and contrast nitroglycerin with nitroprusside  Subset I: Subset II: Warm & Dry Warm & Wet Cardiac index 2.2 Subset III: Subset IV: Cold & Dry Cold & Wet Hold diuretic therapy 18 Pulmonary capillary wedge pressure Assess volume status Hypovolemia Euvolemia (PCWP ≤ 15) (PCWP 15-18) IV fluids Assess BP SBP SBP < 90 mmHg ≥ 90 mmHg No improvement Inotrope Vasodilator (± vasopressor if needed)  Subset I: Subset II: Warm & Dry Warm & Wet Cardiac index 2.2 Subset III: Subset IV: Cold & Dry Cold & Wet 18 Pulmonary capillary wedge pressure Assess SBP SBP < 90 mmHg SBP ≥ 90 mmHg Inotrope No improvement IV diuretic (± vasopressor + if needed) Vasodilator + IV diuretic  Clinical impact ◦ Enhance tissue perfusion through increased myocardial contractility ◦ May increase risk of death  Goals of therapy ◦ Improve CO ◦ Reverse end organ abnormalities  Precautions ◦ Hypotension ◦ Sinus tachycardia ◦ Arrhythmias ◦ In-hospital mortality  Beta-1 and Beta-2-receptor agonist  Increases CO (β1) and decreases SVR (β2)  Pharmacokinetics: ◦ Onset: